a study of venetoclax and abbv-838 combination therapy with dexamethasone in participants with multiple myeloma whose cancer has come back or had no response to recent cancer treatment

Conditions: Multiple Myeloma

Summary: this is an open-label, multicenter clinical trial designed to evaluate the safety and potential efficacy of venetoclax and abbv-838 combination therapy with dexamethasone in participants with relapsed or refractory multiple myeloma (mm) who have received 2 or more prior lines of therapy for multiple myeloma (mm). the study will consist of 2 arms: arm a and arm b (if applicable). each arm will have a dose escalation and dose expansion portion.

the study will consist of 2 arms: arm a and arm b (if applicable). arm a dose escalation will investigate up to 3 doses of abbv-838 at 3-week dosing intervals (q3w) in combination with venetoclax and dexamethasone. arm a dose expansion portion will investigate the abbv-838 q3w dosing interval with venetoclax and dexamethasone at the recommended phase two dose (rptd) combination defined from the dose escalation portion. based on data from the ongoing abbv-838 monotherapy study (study m14-467) arm b dose escalation may be conducted, if deemed necessary. if conducted, arm b dose excalation will investigate up to 3 doses of abbv-838 at either weekly (q1w) or bi-weekly (q2w) dosing intervals in combination with venetoclax and dexamethasone. arm b dose expansion portion will investigate either the abbv-838 q1w or q2w dosing interval in combination with venetoclax and dexamethasone at the rptd combination defined from the dose escalation portion.

Eligibility criteria:
inclusion criteria: * eastern cooperative oncology group (ecog) performance status less than or equal to 1 for participants in the dose escalation portion of the study and ecog less than or equal to 2 in the dose expansion portion. * received at least 2 prior therapies including an immunomodulatory thalidomide derivative compounds (imid) and a proteasome inhibitor. * documented relapsed or progressive multiple myeloma on or after any regimen or is refractory to the most recent line of therapy. * received at least 2 prior therapies including an imid and a proteasome inhibitor. * documented relapsed or progressive multiple myeloma on or after any regimen or is refractory to the most recent line of therapy. * eligible for and agree to bone marrow (bm) aspirate prior to treatment start and at designated times per protocol. * measurable disease at screening, defined as at least one of the following m component in serum (greater than or equal to 0.5 g/dl) and/or urine (greater than or equal to 0.2 g excreted in a 24 hour collection sample) or serum free light chain greater than or equal to 100 mg/dl with an abnormal κ/λ ratio of less than 0.26 or greater than 1.65. exclusion criteria: * received any anti-myeloma therapy (other than monoclonal antibodies), including chemotherapy, radiotherapy, biological, immunotherapy or an investigational therapy, including targeted small molecule agents within 5 half-lives (or 14 days if half-live unknown) prior to first dose of first dose of venetoclax, abbv-838, and dexamethasone. * received anti-myeloma monoclonal antibodies within 6 weeks prior to first dose of venetoclax, abbv-838, and dexamethasone. * has a significant history of renal, neurologic (peripheral neuropathy), psychiatric, endocrinologic (diabetes mellitus), metabolic, immunologic, cardiovascular, pulmonary or hepatic disease within the last 6 months. * received corticosteroid therapy at a dose equivalent to greater than or equal to 4 mg/day of dexamethasone within 3 weeks prior to first dose.

Keywords: lymphoid malignancies next generation sequencing refractory multiple myeloma relapsed multiple myeloma